1. Field
The invention relates to antibody or antigen binding fragment thereof that specifically binds to an epitope in a SEMA domain of c-Met protein, and to pharmaceutical compositions, methods, kits, nucleic acids, and cells related thereto.
2. Description of the Related Art
Hepatocyte growth factor (HGF) is a mesenchyme-derived pleitrophic cytokine that binds the extracellular region of the tyrosine kinase receptor, c-Met, to induce mitogenesis, movement, morphogenesis, and angiogenesis in various normal cells and tumor cells. Regulation of the HGF/c-Met signaling pathway is implicated in various mechanisms related to cancer, such as tumor progression, metastasis, migration, invasion, and angiogenesis. In addition, c-Met amplification or mutation is thought to drive ligand-independent tumorigenesis. Thus, c-Met has recently emerged as a new target for anti-cancer therapy.
In particular, c-Met is known to be involved in induction of resistance to commonly used anti-cancer drugs, and thus, is regarded as an important player in personalized treatments. Representative anti-cancer drugs targeting epidermal growth factor receptor (EGFR) (ERBB1), such as ERBITUX™ (cetuximab) and TARCEVA™ (erlotinib), work by blocking signal transduction related to cancer development. HERCEPTIN™ (trastuzumab), which is a well-known breast cancer drug, targets ERBB2 (HER2) and works by blocking signal transduction necessary for cell proliferation. However, recent findings have indicated that among patients resistant to the drugs described above, anti-cancer drugs do not work due to overexpression of c-Met and activation of other types of signal transduction that leads to cell proliferation. Thus, many pharmaceutical firms are developing anti-cancer drugs to inhibit c-Met.
The related art discloses therapeutic antibody drugs that inhibit the function of c-Met. In this related art, however, antibodies having an original structure induce dimerization of c-Met molecules, thereby causing cancer.
In another related art, which discloses therapeutic antibody drugs that inhibit the function of c-Met, the antibody is capable of inhibiting the binding of c-Met to HGF c-Met, which is a c-Met ligand, but the binding of the antibody to c-Met induces the dimerization of c-Met, independent from the ligand. As a result, the antibody acts as an agonist that induces the transduction of cancer-causing signals.
Another related art discloses, to prevent the dimerization of c-Met, a one-armed antagonistic antibody with respect to c-Met, which is prepared by modifying an agonist, a two-armed antibody, using a genetic recombinant method, and product development in clinical trials is currently under way. However, even in this related art, the antibody works only when the treatment is performed together with chemical therapy, and when the antibody is independently treated, anti-cancer therapeutic effects are proven to be low. Therefore, research into the target on c-Met is needed to develop a novel pharmaceutical composition for preventing or treating cancer that inhibits the function of c-Met.